219823-47-9

Usage

Uses

Used in Pharmaceutical Synthesis:
(R)-3-(p-toluenesulfonyl) oxytetrahydrofuran is used as a chemical reactant for the synthesis of various pharmaceutical agents. Its unique structure and reactivity make it a valuable component in the development of new drugs and medications.
Used in the Synthesis of Anticancer Agents:
In the field of oncology, (R)-3-(p-toluenesulfonyl) oxytetrahydrofuran is used as a key intermediate in the synthesis of anticancer agents. Its incorporation into drug molecules can potentially enhance their efficacy against various types of cancer.
Used in Drug Delivery Systems:
(R)-3-(p-toluenesulfonyl) oxytetrahydrofuran can also be utilized in the development of drug delivery systems, where it may contribute to the improved targeting and release of therapeutic agents, ultimately leading to better treatment outcomes for patients.
Used in the Chemical Industry:
Beyond pharmaceutical applications, (R)-3-(p-toluenesulfonyl) oxytetrahydrofuran may also find use in the broader chemical industry, where it can serve as a building block for the synthesis of various specialty chemicals and materials.

Synthetic route

(R)-3-Hydroxytetrahydrofuran (86087-24-3) + p-toluenesulfonyl chloride (98-59-9) → (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9)

Conditions	Yield
With pyridine In dichloromethane at 0 - 20℃; for 18h; Inert atmosphere;	100%
With potassium iodide; silver(l) oxide In dichloromethane at 40℃;	89%
Stage #1: (R)-3-Hydroxytetrahydrofuran With trimethylamine hydrochloride; triethylamine In dichloromethane at 20℃; for 0.333333h; Stage #2: p-toluenesulfonyl chloride In dichloromethane at 20℃;	83%

4'-hydroxy-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester (121687-76-1) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4'-[(R)-(tetrahydro-furan-3-yl)oxy]-biphenyl-4-carboxylic acid (R)-1-methyl-heptyl ester (1610514-57-2)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 4h;	91.7%

4-ethoxycarbonylpyrazole (37622-90-5) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → C10H14N2O3 (1589005-67-3)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 14h;	91%

4-bromo-phenol (106-41-2) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-3-(4-bromophenoxy)tetrahydrofuran (857854-82-1)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 10h;	90.1%
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 15h;

(2-chloro-5-iodophenyl)(4-hydroxyphenyl)methanone (1459754-40-5) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-(2-chloro-5-iodophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone (915095-87-3)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 50 - 55℃;	87%

(2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-hydroxybenzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (1079083-63-8) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-(((S)-tetrahydrofuran-3-yl)oxy)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-trityl triacetate

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃;	87%

(R)-tert-butyl (2-(5-(2-fluoro-3-hydroxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-2,3-dihydropyrimidine-1(6H)-yl)-1-phenylethyl)carbamate + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → tert-butyl ((R)-2-(5-(2-fluoro-3-(((S)-tetrahydrofuran-3-yl)oxy)phenyl)-3-(2-fluoro- 6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-2,3-dihydropyrimidine-1(6H)-yl)-1-phenylethyl)carbamate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 70℃; for 12h;	87%

C28H30O11 (903566-68-7) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 1,1-anhydro-1-C-[5-(4-((S)-tetrahydrofuran-3-yloxy)-phenyl)-methyl-2-(hydroxymethyl)phenyl]-2,3,4,6-tetra-O-acetyl-β-D-glucopyranose

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 12h;	79%

4-(3-(3-fluoro-4-hydroxyphenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-4-(3-(3-fluoro-4-((tetrahydrofuran-3-yl)oxy)phenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 2h; Inert atmosphere;	77.9%
With caesium carbonate In N,N-dimethyl acetamide; water at 60℃; for 2h;	77.9%

tert-butyl (2R,4R)-4-amino-2-methylpiperidine-1-carboxylate + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → C15H28N2O3

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 95℃; for 48h;	76%

5-(4-fluoro-2-hydroxyphenyl)-9-{2-methyl-2-[3-(trifluoromethyl)phenyl]propanoyl}-1,3,9-triazaspiro[5.5]undecan-2-one + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 5-(4-fluoro-2-{[(3S)-oxolan-3-yl]oxy}phenyl)-9-{2-methyl-2-[3-(trifluoromethyl)phenyl]propanoyl}-1,3,9-triazaspiro[5.5]undecan-2-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 5h;	74%

4-hydroxy-benzaldehyde (123-08-0) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-4-((tetrahydrofuran-3-yl)oxy)benzaldehyde

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 100℃; for 14h;	70%

methyl 3-hydroxy-5-(5-methyl-1,3-thiazol-2-yl)benzoate + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → methyl 3-(5-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 90℃; for 36h;	67%

3-bromo-5-hydroxy-benzoic acid methyl ester (192810-12-1) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → methyl 3-bromo-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃;	67%

6-(4-hydroxy-1,2-dihydrofuro[3,2-f]quinolin-9-yloxy)-N-methyl-1-naphthamide + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-6-((4-((tetrahydrofuran-3-yl)oxy)-1,2-dihydrofuro[3,2-f] quinolin-9-yl)oxy)-Ν-methyl-1-naphthamide

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 0.5h; Inert atmosphere;	67%

4-bromo-3-methoxyphenol (102127-34-4) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → C11H13BrO3

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 80℃; for 16h;	64%

GSK333081 + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 1-isopropyl-3-(β-D-glucopyranosyloxy)-4-[4-((S)-tetrahydrofuran-3-yloxy)benzyl]-5-methyl-1H-pyrazole

Conditions	Yield
With caesium carbonate In DMF (N,N-dimethyl-formamide) at 50℃; for 16h;	60%

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (864070-37-1) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → empagliflozin (864070-44-0)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 21h;	57%
With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 18h;	49%
With caesium carbonate In N,N-dimethyl-formamide at 75℃; for 18h;	49%
With caesium carbonate at 25 - 40℃;
With caesium carbonate In N,N-dimethyl-formamide at 30 - 45℃; for 24h;	0.55 kg

4-bromo-2(1H)-pyridinone (36953-37-4) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4-bromo-1-[(S)-tetrahydro-furan-3-yl]-1H-pyridin-2-one (1237534-49-4) + 4-bromo-2-[(S)-tetrahydro-furan-3-yloxy]-pyridine (1237534-50-7)

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 80℃;	A 16% B 56%
With potassium carbonate In dimethyl sulfoxide at 80℃;

4-(3-(6-hydroxypyridin-3-yl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (S)-4-(4,4-dimethyl-5-oxo-3-(6-((tetrahydrofuran-3-yl)oxy)pyridin-3-yl)-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile

Conditions	Yield
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 2h; Inert atmosphere;	52.6%
With caesium carbonate In N,N-dimethyl acetamide at 60℃; for 2h;	52.6%

4-(4-(methoxymethyl)-2-((1s,4s)-4-methylcyclohexylamino)-6-(oxetan-3-yloxy)pyrimidin-5-yl)phenol + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4-(methoxymethyl)-N-((1s,4s)-4-methylcyclohexyl)-6-(oxetan-3-yloxy)-5-(4-((S)-tetrahydrofuran-3-yloxy)phenyl)pyrimidin-2-amine

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 20℃;	52%

5-(4-fluoro-2-hydroxyphenyl)-9-{[2-(trifluoromethoxy)phenyl]acetyl}-1,3,9-triazaspiro[5.5]undecan-2-one + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 5-(4-fluoro-2-{[(3S)-oxolan-3-yl]oxy}phenyl)-9-{[2-(trifluoromethoxy)phenyl]acetyl}-1,3,9-triaza-spiro[5.5]undecan-2-one

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 5h;	52%

(2S,3R,4R,5S,6R)-2-(3-(4-hydroxybenzyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (333360-66-0) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 1-methyl-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-4-(β-D-glucopyranos-1-yl)-benzene (892486-47-4)

Conditions	Yield
With caesium carbonate In N,N-dimethyl-formamide at 60 - 80℃; for 22h;	46%

6-(3-azabicyclo[3.1.0]hexan-6-yl)-5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 5-methyl-1-(tetrahydro-2H-pyran-2-yl)-6-(3-((S)-tetrahydrofuran-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-indazole

Conditions	Yield
With potassium carbonate at 110℃; for 16h;	40%

(R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) + 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (269409-70-3) → 2-(4-((S)-tetrahydrofuran-3-yloxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1416157-64-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 85℃; for 15h;	30%

4-(4-methyl-2-((1s,4s)-4-methylcyclohexylamino)-6-(oxetan-3-yloxy)pyrimidin-5-yl)phenol + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → 4-methyl-N-((1S,4S)-4-methylcyclohexyl)-6-(oxetan-3-yloxy)-5-(4-((S)-tetrahydrofuran-3-yloxy)phenyl)pyrimidin-2-amine

Conditions	Yield
With caesium carbonate; potassium iodide In N,N-dimethyl-formamide at 20 - 90℃; for 4.5h;	30%

(6aS,8S)-4-iodo-6a,7,8,9-tetrahydro-6H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazin-8-ol + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (6aS,8S)-4-iodo-8-(((S)-tetrahydrofuran-3-yl)oxy)-6a,7,8,9-tetrahydro-6H-pyrido[3,2-b]pyrrolo[1,2-d][1,4]oxazine

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0 - 20℃; Inert atmosphere;	28.68%

4-carbethoxypiperidine (1126-09-6) + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → ethyl 1-[(3S)-tetrahydrofuran-3-yl]piperidine-4-carboxylate

Conditions	Yield
With potassium carbonate In acetonitrile at 70℃; for 24h;	27%

(1R,4R)-5-(6-(6-(3-azabicyclo[3.1.0] hexan-6-yl)-5-methyl-1H-indazol-1-yl)-2-methylpyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane + (R)-tetrahydrofuran-3-yl 4-methylbenzenesulfonate (219823-47-9) → (1R,4R)-5-(2-methyl-6-(5-methyl-6-(3-((S)-tetrahydrofuran-3-yl)-3-azabicyclo[3.1.0] hexan-6-yl)-1H-indazol-1-yl)pyrimidin-4-yl)-2-oxa-5-azabicyclo[2.2.1]heptane

Conditions	Yield
With potassium carbonate In acetonitrile at 110℃; for 24h; Inert atmosphere;	19%

Upstream product

• 86087-24-3 (R)-3-Hydroxytetrahydrofuran 
• 98-59-9 p-toluenesulfonyl chloride 

Downstream Products

• 915771-22-1 methyl 3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzoate 
• 915095-87-3 (S)-(2-chloro-5-iodophenyl)(4-((tetrahydrofuran-3-yl)oxy)phenyl)methanone 
• 892486-47-4 1-methyl-2-[4-((S)-tetrahydrofuran-3-yloxy)-benzyl]-4-(β-D-glucopyranos-1-yl)-benzene 
• 915771-03-8 N-(1-methyl-1H-pyrazol-3-yl)-3-[(phenylmethyl)oxy]-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide 
• 864070-44-0 empagliflozin 
• 915095-99-7 (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-(((S)-tetrahydrofuran-3-yl)oxy)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-trityl triacetate 

Relevant academic research and scientific papers

5-OXA-2-AZASPIRO[3.4]OCTANE DERIVATIVES AS M4 AGONISTS

Provided herein are compounds according to Formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R5, and R7 are defined herein. Also provided herein are pharmaceutical compositions comprising a compound of Formula (I) as well as the use of such compounds as M4 receptor agonists.

Design and Synthesis of Pyrrolo[2,3-d]pyrimidine-Derived Leucine-Rich Repeat Kinase 2 (LRRK2) Inhibitors Using a Checkpoint Kinase 1 (CHK1)-Derived Crystallographic Surrogate

Inhibitors of leucine-rich repeat kinase 2 (LRRK2) and mutants, such as G2019S, have potential utility in Parkinson’s disease treatment. Fragment hit-derived pyrrolo[2,3-d]pyrimidines underwent optimization using X-ray structures of LRRK2 kinase domain surrogates, based on checkpoint kinase 1 (CHK1) and a CHK1 10-point mutant. (2R)-2-Methylpyrrolidin-1-yl derivative 18 (LRRK2 G2019S cKi0.7 nM, LE 0.66) was identified, with increased potency consistent with an X-ray structure of 18 /CHK1 10-pt. mutant showing the 2-methyl substituent proximal to Ala147 (Ala2016 in LRRK2). Further structure-guided elaboration of 18 gave the 2-[(1,3-dimethyl-1H-pyrazol-4-yl)amino] derivative 32 . Optimization of 32 afforded diastereomeric oxolan-3-yl derivatives 44 and 45 , which demonstrated a favorablein vitroPK profile, although they displayed species disconnects in thein vivoPK profile, and a propensity for P-gp- and/or BCRP-mediated efflux in a mouse model. Compounds 44 and 45 demonstrated high potency and exquisite selectivity for LRRK2 and utility as chemical probes for the study of LRRK2 inhibition.

Fused tricyclic derivative as FGFR4 inhibitor

The present invention provides a fused tricyclic derivative that is the selective inhibitor of fibroblast growth factor receptor 4 (FGFR4), a pharmaceutical composition containing the compound, a method of making the compound and a method of treating cell proliferative diseases, such as cancer, using the compounds of the invention.

TROPOLONE DERIVATIVES AND TAUTOMERS THEREOF FOR IRON REGULATION IN ANIMALS

Disclosed are a series of compounds or their tautomers having a general structure represented by Formula (la), (lb), (Ila), (lIb), or (lIc) and pharmaceutically acceptable salts thereof. The present disclosure also relates to pharmaceutical compositions comprising said compounds or tautomers. The present disclosure further relates to a method of treating a disease or condition associated with iron dysregulation or dysfunctional iron homeostasis comprising administering to a subject in need thereof a therapeutically effective amount of Formula (la), (lb), (Ila), (lIb), or (lIc) compounds or tautomers.

8-substituted styryl xanthine derivative and application thereof

The invention discloses an 8-substituted styryl xanthine derivative and application thereof, and particularly relates to a novel 8-substituted styryl xanthine derivative and a pharmaceutical composition containing the compound, and the 8-substituted styryl xanthine derivative can be used as a selective adenosine A2A receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition, and application of the compound and the pharmaceutical composition in preparation of drugs for treating adenosine A2A receptor related diseases, especially Parkinson's disease.

Nitrogen-containing fused tricyclic derivative and application thereof

The invention discloses a nitrogen-containing fused tricyclic derivative and application thereof, and particularly relates to a novel nitrogen-containing fused tricyclic derivative and a pharmaceutical composition containing the nitrogen-containing fused tricyclic derivative, and the nitrogen-containing fused tricyclic derivative can be used as a selective adenosine A2A receptor antagonist. The invention also relates to a method for preparing the compound and the pharmaceutical composition and application of the compound and the pharmaceutical composition in preparation of drugs for treating adenosine A2A receptor related diseases, especially Parkinson's disease.

PYRAZOLOPYRIDINE DERIVATIVE HAVING GLP-1 RECEPTOR AGONIST EFFECT

The present invention provides a compound having the basic structure shown by Formula (I) in which the indole ring and the pyrazolopyridine structure is bound through a substituent, a salt thereof or a solvate of either the compound or a salt of the compound, as well as a preventative agent or a therapeutic agent for non-insulin-dependent diabetes mellitus (Type 2 diabetes) or obesity containing such compound, salt or solvate as an active ingredient.

FUSED RING PYRIMIDINE COMPOUND, INTERMEDIATE, AND PREPARATION METHOD, COMPOSITION AND USE THEREOF

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N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicine for treating diabetes

The invention discloses an N-aryl-1-deoxynojirimycin derivative and application thereof in preparing of medicines for treating diabetes. The structural formula of the derivative is as shown in the specification, and in the formula, R1 is halogen or C1-C4 alkyl; R2 is substituted aryl; R3 is H or acyl with 1-4 atoms. The compound disclosed by the invention has functions of remarkably reducing blood sugar and promoting discharge of glucose from urea, and can be used for preparing medicines for treating diabetes.

SOLID STATE FORMS OF EMPAGLIFLOZIN

The present invention provides solid state forms of empagliflozin, complexes of empagliflozin with amino acids, processes for their preparation and their use in purification of empagliflozin and also provided pharmaceutical compositions comprising them and their use in therapy (Formula I).